What is the management plan for a patient with a gastrointestinal (GI) bleed on Apixaban (apixaban)?

Management of Gastrointestinal Bleeding in Patients on Apixaban

For patients with gastrointestinal bleeding while on apixaban, immediately stop the anticoagulant, provide local therapy and supportive care, and consider administering andexanet alfa for severe or life-threatening bleeding. 1

Initial Assessment and Classification

• Stratify patients as hemodynamically stable or unstable (unstable defined as shock index >1) to determine management urgency 1
• For stable patients, categorize the bleed as major or non-major 1:
  • Major: Bleeding at a critical site, hemodynamic instability, or clinically overt bleeding with hemoglobin decrease ≥2 g/dL or requiring ≥2 units of RBC transfusion 1
  • Non-major: Bleeding that doesn't meet major bleeding criteria 1

Immediate Management

For Major/Severe GI Bleeding:

• Stop apixaban immediately 1
• Provide supportive care and volume resuscitation 1
• Consider administering andexanet alfa, a specific reversal agent for apixaban 1, 2
• If andexanet alfa is unavailable, consider prothrombin complex concentrate (PCC) or activated PCC 1, 2
• For recent ingestion (within 2-4 hours), consider activated charcoal to reduce absorption 1, 2
• Discontinue any concomitant antiplatelet agents 1
• Assess for and manage comorbidities that could contribute to bleeding (e.g., thrombocytopenia, uremia, liver disease) 1

For Non-Major GI Bleeding:

• Consider continuing apixaban if the bleeding is minor and self-limiting 1
• Provide local therapy and supportive measures 1
• If on concomitant antiplatelet therapy, assess risks and benefits of stopping 1

Transfusion Management

• Use restrictive RBC transfusion thresholds (Hb trigger 70 g/L and target 70-90 g/L) 1
• For patients with cardiovascular disease, use a higher threshold (Hb trigger 80 g/L and target 100 g/L) 1

Diagnostic Workup

• For hemodynamically unstable patients or those with active bleeding, CT angiography is recommended to localize the bleeding site 1
• If no source is identified on CT angiography and the patient is unstable, perform immediate upper endoscopy 1
• For stable patients with major bleeding, admit for colonoscopy 1

Considerations for Restarting Anticoagulation

After bleeding has been controlled, determine if there's a clinical indication for continued anticoagulation 1. Consider the following factors:

• Was the bleed at a critical site? 1
• Is the patient at high risk of rebleeding or death/disability with rebleeding? 1
• Has the source of bleeding been identified and treated? 1
• Are surgical or invasive procedures planned? 1
• What is the patient's thrombotic risk? 1, 3

Timing of Anticoagulation Resumption:

• For patients with high thrombotic risk (e.g., mechanical heart valve, atrial fibrillation with valve disease, recent venous thromboembolism), consider resuming anticoagulation within 7 days after bleeding has stopped 1
• For patients with low thrombotic risk, consider delaying anticoagulation restart until the risk of rebleeding is minimal 1, 3

Prevention of Recurrent Bleeding

• Reassess the appropriate dosing of apixaban based on patient's age, weight, and renal function 2
• Consider reducing the dose by 50% when apixaban is coadministered with drugs that are combined P-gp and strong CYP3A4 inhibitors 2
• Evaluate concomitant medications that increase bleeding risk (NSAIDs, antiplatelet agents, SSRIs) 2, 4
• For patients on aspirin for primary prevention, consider permanent discontinuation 1
• For patients on aspirin for secondary prevention, restart as soon as hemostasis is achieved 1

Important Caveats

• Premature discontinuation of apixaban without adequate alternative anticoagulation increases the risk of thrombotic events 2
• The pharmacodynamic effect of apixaban can persist for at least 24 hours after the last dose 2
• Hemodialysis does not significantly reduce apixaban levels due to high protein binding 2
• Unlike warfarin, vitamin K administration does not reverse the anticoagulant effect of apixaban 2
• Monitoring for the anticoagulation effect of apixaban using standard clotting tests (PT, INR, or aPTT) is not useful 2